1. Field of the Invention
This invention relates to the use of peracylated cyclodextrin in a pharmaceutical composition, and more specifically, relates to a pharmaceutical composition wherein a per-C.sub.2-18 acylated cyclodextrin is used as a drug carrier, and further to a process for preparing such a composition having a specified form.
2. Description of Prior Arts
Cyclodextrin (hereinafter, referred to as CyD) is an oligosaccharide wherein glucose residues are cyclically bound through .alpha.-1,4 bond. Those which are each composed of 6, 7 or 8 glucose residues and each of which is called .alpha., .beta. or .gamma.-CyD respectively have been put to practical use. These CyDs have a high clathrating ability on certain chemical substances, and are utilized, in the field of pharmaceuticals, food and cosmetics, for various uses such as stabilization, retention of volatile substances and solubilization of substances which are sparingly soluble or insoluble in water.
Further, for the purpose of utilizing such physicochemical characteristics and clathrating ability of CyD as a multifunctional drug carrier, etc., various CyD derivatives are provided. For example, partially acylated cyclodextrin for solubilizers, preparation aids, stabilizing agents, degreasing agents, solvent-substitutes, and further, coating materials, fixing aids, phase transfer catalysts and masking agents on the sense of taste and the sense of smell are described in Japanese Laid-Open (Kokai) Patent Publication No. 35 300501/1995.
Furthermore, there can be taken, as noteworthy compounds, heptakis (2,3,6-tri-0-acetyl)-.beta.-cyclodextrin and octakis (2,3,6-tri-0-acetyl)-.gamma.-cyclodextrin for use in combination with an water-soluble drug described in K. Uekawa et al., J. Controlled Release, 31 (1994), 173-180, and peracylated .beta.-cyclodextrins described in J. Pharm. Pharmacol. 1994, 46: 714-717; Chem. Pharm. Bull. 43 (1995), 130-136 and Pharmaceutical Science 1995, 1: 517-520. As for these peracylated .beta.-cyclodextrins, there have been disclosed those having acyl groups having 2 to 12 carbon atoms, among which some that have a certain chain length can be used in combination with a water-soluble drug such as morsidomine or salbutamol to form a preparation which is interesting in that, when orally administered to experimental animals, it allows the release rate of the drug to be controlled. In the above J. Pharm. Pharmacol. 1994, 46: 714-717, it is shown that particularly, perbutanoyl (C.sub.4)-.beta.-CyD remarkably retards the drug release rate, compared with other aclated .beta.-CyDs. It has been suggested that this action is caused by the appropriate adhesion to mucosa and hydrophobicity of perbutanoyl-.beta.-CyD.
On the other hand, attention has been drawn in recent years to the development of pharmaceuticals for the trans-mucosal or transdermal administration of drugs which have systemic or topical actions toward various diseases, with a view to decreasing compliance of patients. However, since it is difficult to control the release of drugs from pharmaceuticals, it has been necessary to use various additives or, in the case of solid drugs, to employ a solvent to dissolve the solid drugs with. Further, there is a case where it is necessary to select additives to be compounded for the purpose of controlling the release of drug or promoting its absorption or solvents for dissolving the drug. These materials are, however, generally irritative to skin or cutis, thus causing problems that long-term use is difficult. Particularly. many of absorption enhancers for drugs have generally a high solubility in lipid, and it is said that almost all of the above absorption enhancers interact with the adhesives in transdermal absorption compositions, with the result that adhesion or adhesive force between the pharmaceuticals and the cutis is adversely influenced (Development of Pharmaceuticals, 12, page 374, Chapter 3 Pharmaceutical Materials Expectable in New Functions, published by Hirokawa Shoten in 1988).
In order to overcome these problems, it has been proposed to place a drug reservoir and an absorption enhancer reservoir separately, or there has been proposed a peripheral-type pharmaceuticals for transdermal absorption wherein the adhesives are placed only at the periphery, as in tranzone, and, thus, certain results have been attained.
However, there are still needs for a composition for trans-mucosal or transdermal administration which is easy to prepare, excellent in drug releasability from the pharmaceutical composition and excellent in absorptivity in a living body of the released drug. Thus, the object of the invention lies in providing a pharmaceutical composition satisfying the above needs.